Alejandro Santos

Low-dose oral contraceptives and 24-hour ambulatory blood pressure

Objective: To evaluate in normotensive women the influence of low‐dose oral contraceptives (OC, monophasic formulations containing 30 μg of estrogen) on 24‐h blood pressure. Methods: We evaluated prospectively in 15 normotensive healthy women (three smokers) the influence of OC on 24‐h ambulatory blood pressure monitoring (ABPM). ABPM was performed (SpaceLabs 90207) before and after 6–9 months of use of OC. We also evaluated ABPM in eight women (two smokers) before and after 6–8 months on an intrauterine device (IUD) as contraceptive method — these were used as control subjects. Results: OC produced a significant increase in 24‐h ABPM values (from 120±3/75±2 to 128±4/81±2 mmHg, P<0.04) which was particularly evident for night‐time values (from 108±2/64±2 to 120±4/73±2 mmHg, P<0.02). After OC, two normotensive women developed ‘hypertensive values’. In OC users there was a slight but significant increase in body weight which did not correlate with the increase of blood pressure. In contrast, in the control group (IUD) neither ABPM values nor weight were modified by the contraceptive maneuver. Conclusions: In normotensive women, low‐dose OC may increase blood pressure to an extent that, at least in some women, may affect blood pressure control towards ‘hypertensive values’. This stresses the importance of monitoring blood pressure values during OC treatment.

Deficiency of renal dopaminergic-dependent natriuretic response to acute sodium load in black salt-sensitive subjects in contrast to salt-resistant subjects

OBJECTIVE To evaluate the involvement of the renal dopaminergic system in the natriuretic responses to acute saline load in salt-resistant (SR) and salt-sensitive (SS) black normotensive (NT) and hypertensive (HT) subjects. DESIGN AND METHODS We studied the relationship between the urinary excretion of dopa, dopamine (DA) and its metabolite DOPAC and the natriuretic responses to acute volume expansion (2 l NaCl 0.9% over 2 h) in 20 black NT subjects (12 SR and 8 SS) and 19 black HT subjects (10 SS and 9 SR). Subjects received a low salt (LS) diet (40 mmol sodium/day) for 1 week and a high salt (HS) diet (300 mmol sodium/day) for 1 week; the sequence of the dietary regimens was randomized. Comparisons were made between the results before the saline infusion (baseline) and the results 2 h after the infusion. RESULTS In all the groups saline infusion induced significant increases in urinary volume (ml/4 h) of two- to three-fold and in urinary sodium excretion (mmol/4 h) of three- to ten-fold; these increases were significantly greater during the HS diet than during the LS diet. Saline infusion significantly increased the mean arterial pressure (MAP) by 5 mmHg in HT-SS subjects and by 4-5 mmHg in NT-SS subjects, but the MAP did not changed in the NT-SR and HT-SR groups. Under the LS diet, saline infusion changed the DA excretion (in nmol/4 h) by -49+/-89 in HT-SS subjects, by 17+/-52 in NT-SS subjects, by 235+/-72 in HT-SR subjects and by 220+/-86 in NT-SR subjects (P < 0.05 between SR and SS subjects). The saline infusion-induced changes in DA excretion correlated significantly with the increases in urinary sodium excretion (r = 0.71, P < 0.01) in the NT-SR and HT-SR subjects under the LS diet, but not in the SR groups on the HS diet nor in the SS groups (HT and NT) on either diet. Saline infusion significantly reduced the DA/dopa ratio in SS (NT and HT) but not SR (NT and HT) subjects, whereas the DA/DOPAC (dihydroxyphenylacetic acid) ratios were similar in all the groups. CONCLUSIONS The urinary dopaminergic system may participate in the natriuretic responses to acute sodium load only in SR subjects (NT and HT) and only under LS diets, but not in SS subjects (NT and HT). This strongly suggests that black NT- and HT-SS subjects have an underlying impairment in the activity of the renal dopaminergic system which may be associated with a reduced decarboxylation of dopa into DA.

arterial distensibility in subjects with white-coat hypertension with and without diabetes or dyslipidaemia: comparison with normotensives and sustained hypertensives

Background Arterial distensibility can be assessed by measuring pulse‐wave velocity (PWV). Objective To determine whether diabetes, smoking and dyslipidaemia were associated with greater than normal stiffness of aortic walls in subjects with white‐coat hypertension. Methods Arterial distensibility was assessed by automatic measurement of carotid‐femoral PWV in 35 healthy normotensives, 46 white‐coat hypertensives (WCH, clinic blood pressures > 140/90 mmHg, daytime blood pressures < 130/85 mmHg) and 81 ambulatory hypertensives (clinic blood pressures > 140/90 mmHg, daytime blood pressures ≥ 130 mmHg systolic or ≥ 85 mmHg diastolic, or both) all matched for age, sex and body mass index. Nineteen normotensives (subgroup A), 28 WCH (subgroup A) and 37 ambulatory hypertensives (subgroup A) had only one or no other major cardiovascular risk factor whereas 16 normotensives (subgroup B), 18 WCH (subgroup B) and 44 ambulatory hypertensives (subgroup B) had also some combination of non‐insulin‐dependent diabetes, a smoking habit and dyslipidaemia. Results Both for the WCH and for ambulatory hypertensives diabetes and dyslipidaemia (subgroups B) were associated with higher (P < 0.04) PWV (11.6 ± 0.3 and 12.8 ± 0.3 m/s, respectively) than for subgroups A (9.3 ± 0.5 and 10.9 ± 0.6 m/s, respectively). In contrast, PWV for WCH in subgroup A (9.3 ± 0.5 m/s) did not differ (P > 0.35) from those for the normotensive subgroups A (9.2 ± 0.3 m/s) and B (9.6 ± 0.4 m/s). PWV was not correlated to levels of glycaemia, glycosylated haemoglobin and cholesterolaemia. Conclusions These results suggest that, both for ambulatory hypertensives and for WCH, diabetes and dyslipidaemia are associated with an impairment of arterial distensibility that can entail a greater than normal cardiovascular risk, which might dictate a more than usually stringent treatment of concomitant risk factors and possibly of high blood pressure. In contrast, PWV in WCH of the subgroup A did not differ from those in normotensives, reinforcing the hypothesis that WCH is associated with a benign cardiovascular outcome in the absence of other cardiovascular risk factors.

Differences in behavior profile between normotensive subjects and patients with white-coat and sustained hypertension

It has been hypothesized that white-coat hypertensives (WCHs) have lower cardiovascular risk than sustained hypertensives (HTs), but higher emotional reactivity. We evaluated 92 HT patients (clinic and daytime BP>140/90 mmHg), 52 WCHs (clinic BP>140190 and ambulatory daytime BP<134/ 85 mmHg), and 74 normotensive subjects (NTs, clinic BP<140/90 and ambulatory daytime BP<134/85 mmHg), aged between 24 and 72 years, and matched for educational level, age, gender, and weight for depression, psychopathology, well-being, and quality of life. HTs showed worse scores than WCHs and NTs on most of the psychological variables; no differences were found between WCHs and NTs except on physical mobility. Daytime BP variability was HTs>WCHs>NTs, whereas nighttime BP variability was HTs>WCHs=NTs. We conclude that HTs have worse psychological profiles than the other two groups. WCHs and NTs have similar psychological profiles, although WCHs have a higher daytime BP variability, which is not associated with higher emotional reactivity.

Acute hypotensive, natriuretic, and hormonal effects of nifedipine in salt-sensitive and salt-resistant black normotensive and hypertensive subjects.

In a randomized double-blind study, we compared the short-term effects of nifedipine (10 mg 3x daily for 1 day) versus placebo on 24-h blood pressure, diuresis, natriuresis, urinary excretion of dopamine and metabolites, and on plasma renin activity (PRA) and plasma aldosterone levels in 18 black hypertensive (HT) patients [eight salt-resistant (HT-SR) and 10 salt-sensitive (HT-SS)], and in 20 black normotensive (NT) subjects (12 NT-SR and eight NT-SS) who were studied randomly with both a high- (HS) and a low-salt (LS) diet. In comparison to placebo, nifedipine significantly decreased 24-h mean BP in all groups either with HS or LS diets (all p<0.05). With HS, greater hypotensive effects were achieved in NT-SS (-10+/-2 mm Hg) versus NT-SR (-3+/-1 mm Hg; p<0.05) and in HT-SS (-18+/-2 mm Hg) versus HT-SR (-12+/-2 mm Hg; p<0.05). In NT-SS and HT-SS, nifedipine induced greater (p<0.05) BP decrease with HS (-10+/-2 and -18+/-2 mm Hg) than with LS (-4+/-1 and -9+/-1 mm Hg, respectively), whereas in NT-SR and HT-SR, the hypotensive effect did not differ between HS and LS. Nifedipine versus placebo significantly increased natriuresis and fractional excretion of sodium in all groups only with HS (p<0.05) but not with LS diets. Only in HT-SS were the hypotensive and natriuretic effects of nifedipine significantly correlated (r = -0.77; p<0.01). Nifedipine produced a similar increase of the urinary excretion of dopamine, L-DOPA, and of DOPAC in all subjects, which did not correlate with hypotensive and natriuretic effects. Nifedipine did not modify plasma levels of renin and of aldosterone except in NT-SS with HS, in whom nifedipine increased PRA levels (p <0.05). We conclude that although nifedipine reduces BP in all groups of NT and HT with LS and HS diets, the effect is greater in salt-sensitive subjects with HS. Although in HT-SS with HS, the short-term natriuretic response to nifedipine may contribute to its hypotensive effects, the diuretic-natriuretic effect of nifedipine is not necessary for the expression of its hypotensive effect. Moreover, it is unlikely that any short-term effects of nifedipine either on the renal dopaminergic system or on the secretion of aldosterone explain nifedipine short-term hypotensive and diuretic-natriuretic effects.

Accuracy of twenty-four-hour ambulatory blood pressure monitoring (night-day values) for the diagnosis of secondary hypertension

Objectives To determine the accuracy of 24-h ambulatory blood pressure monitoring, using the relationship between night-time and daytime values, in diagnosing secondary hypertension. Patients and methods A prospective study was performed in a referred population of 402 hypertensive patients (clinic systolic/diastolic blood pressure >140/90 mmHg). The ambulatory monitoring data included 24-h mean, awake (daytime) and sleeping (night-time) values. Secondary hypertension was diagnosed by standard procedures. To describe the accuracy of ambulatory blood pressure monitoring, receiver–operator characteristic curves were constructed, using sensitivity and specificity values for deciles of the distribution of overnight blood pressure falls (absolute and percentage). Measurements included the fall in nocturnal blood pressure, sensitivity (the percentage of those with secondary hypertension who were classified as non-dippers), specificity (the percentage of non-secondary hypertensives who were classified as dippers) and predictive values of ambulatory blood pressure monitoring. Results On average, overnight systolic/diastolic blood pressure fell in primary hypertensives (n = 290) by 20/18 mmHg (13%/19%), in white-coat hypertensives (n = 65, daytime ambulatory blood pressure <135/87 mmHg) by 17/15 mmHg (13%/19%) and in patients with secondary hypertension (n = 47, renal/renovascular and endocrine forms) by 13/11 mmHg (9%/12%). From receiver–operator characteristic curves, the nocturnal blood pressure fall of 15 mmHg showed the highest accuracy, with a sensitivity/specificity of 61%/69% (systolic) and 75%/62% (diastolic) whereas 10% (systolic) and 15% (diastolic) nocturnal falls had a sensitivity/specificity of 62%/74% (systolic) and 62%/70% (diastolic). The ambulatory blood pressure data had a high (>93%) negative predictive value for secondary hypertension. Conclusions Secondary hypertension is associated with a blunted nocturnal fall in blood pressure. Ambulatory blood pressure monitoring data are not critically important for the diagnosis and screening of secondary hypertension but may be helpful in excluding it.

Nutritional Strategies Facing an Older Demographic: The Nutrition UP 65 Study Protocol

Background The population of Portugal is aging. The lack of data on older adults’ nutritional status and the lack of nutrition knowledge amongst health professionals, caregivers, and older adults themselves, remains a challenge. Objective The Nutrition UP 65 study aims to reduce nutritional inequalities in the older Portuguese adult population and improve knowledge regarding older Portuguese adults’ nutritional status, specifically relating to undernutrition, obesity, sarcopenia, frailty, hydration, sodium, and vitamin D statuses. Methods A representative sample of older Portuguese adults was selected. Sociodemographic, lifestyle, anthropometric, functional, and clinical data were collected. Sodium excretion, hydration, and vitamin D statuses were assessed. Results Data collection (n=1500) took place between December, 2015 and June, 2016. Results will be disseminated in national and international scientific journals, and via Portuguese media. Conclusions Nutrition UP 65 results will provide evidence for the design and implementation of effective preventive public health strategies regarding the elderly. These insights may represent relevant health gains and costs savings.

Relevance of a Hypersaline Sodium-Rich Naturally Sparkling Mineral Water to the Protection against Metabolic Syndrome Induction in Fructose-Fed Sprague-Dawley Rats: A Biochemical, Metabolic, and Redox Approach

The Metabolic Syndrome increases the risk for atherosclerotic cardiovascular disease and type 2 Diabetes Mellitus. Increased fructose consumption and/or mineral deficiency have been associated with Metabolic Syndrome development. This study aimed to investigate the effects of 8 weeks consumption of a hypersaline sodium-rich naturally sparkling mineral water on 10% fructose-fed Sprague-Dawley rats (Metabolic Syndrome animal model). The ingestion of the mineral water (rich in sodium bicarbonate and with higher potassium, calcium, and magnesium content than the tap water used as control) reduced/prevented not only the fructose-induced increase of heart rate, plasma triacylglycerols, insulin and leptin levels, hepatic catalase activity, and organ weight to body weight ratios (for liver and both kidneys) but also the decrease of hepatic glutathione peroxidase activity and oxidized glutathione content. This mineral-rich water seems to have potential to prevent Metabolic Syndrome induction by fructose. We hypothesize that its regular intake in the context of modern diets, which have a general acidic character interfering with mineral homeostasis and are poor in micronutrients, namely potassium, calcium, and magnesium, could add surplus value and attenuate imbalances, thus contributing to metabolic and redox health and, consequently, decreasing the risk for atherosclerotic cardiovascular disease.

Changes in rat cerebral mitochondrial succinate dehydrogenase activity after brain trauma

The objective of this study was to evaluate 2,3,5-triphenyltetrazolium chloride (TTC) staining in the brain tissue of rats submitted to a closed head traumatic injury, in comparison to control rats not submitted to trauma. The closed head, weight drop trauma model described by Marmarou et al. (1994) was used. Animals were all sacrificed 24 h after trauma. Staining of cerebral coronal slices using TTC, coupled to image analysis software, was used to measure the level of staining. An ultrastructural study of the brain region underneath the impact zone, as well as from the correspondent region of control rats, was also done. The TTC image analysis revealed a significant decrease in the percentage of white area, in traumatized rats (mean ± SEM 23.93% ± 2.26, n = 4 for control, 12.13% ± 1.72, n = 9 for traumatized rats, p < .05). The ultrastructural analysis revealed that the number of axons showing at least one mitochondrion was significantly higher in the trauma group (mean ± SEM 49.3%, n = 4 rats, 75 photographs, 2443 axons) than in control groups (23%, n = 3 rats, 30 photographs, 6220 axons (p < .001). Another difference observed was the larger mitochondrial size in the axons of traumatized rats (mean diameter ± SEM 0.520 ± 0.003 μm) compared to the controlled rats (0.368 ± 0.006 μm; p < .001). The ultrastructural observation of the traumatized brain revealed a significantly higher number of peroxisomes per photograph (mean number ± SEM 10.58 ± 1.18, n = 75) compared to the control group (0.19 ± 0.08, n = 30, p < .001). The results indicate an increase of mitochondrial and peroxysomal relative mass, with a higher succinate dehydrogenase activity, 24 h after the induction of traumatic brain injury

Anti-Angiogenic Properties of Cafestol and Kahweol Palmitate Diterpene Esters

Epidemiological studies support the association of coffee‐specific diterpenes, with various beneficial health effects. Although anti‐antiangiogenic properties of free cafestol and kahweol have been recently described, available data regarding their esterified form, in particular palmitate esters as the main diterpene esters present in coffee, are still rare. Given that angiogenesis plays an important role in many pathological conditions, including cancer growth and metastasis, this study aimed to assess and compare the potential anti‐angiogenic effects of cafestol palmitate (CP) and kahweol palmitate (KP) in an in vitro angiogenesis model. According to our findings, both compounds inhibited angiogenesis steps on human microvascular endothelial cells (HMVECs), although a more significant effect was observed for KP. Compared to control, HMVECs viability decreased in a dose‐dependent manner upon incubation either with CP or KP. Concentrations of 75 and 100 μM of each compound were cytotoxic. Cell proliferation was also dramatically reduced by both diterpene esters at 50 μM, although KP had a stronger inhibitory effect. However, CP and KP did not induce apoptosis on HMVECs. Both compounds reduced cell migration, but this effect was only statistically significant after KP incubation. Inhibition of VEGFR2 expression and its downstream effector Akt, but not Erk, was also observed in CP‐ and KP‐treated HMVECs. These findings were confirmed using ELISA assay for phosphorylated (active) VEGFR‐2. Taken together, these data indicate that both CP and KP can be considered potent compounds against angiogenesis‐dependent disorders. Our findings further indicate that KP exerts more potent anti‐angiogenic effects than CP, in most of assays. J. Cell. Biochem. 117: 2748–2756, 2016.